Studies on the in vivo and microsome-catalyzed in vitro covalent binding of dioxane (14C-labeled) to macromolecules and nucleotides will be continued and these studies will now include p-dioxane-2-one, the recently discovered major urinary metabolite of dioxane. Since the metabolite shows considerably higher acute toxicity than dioxane, the in vitro metabolism of dioxane to p-dioxane-2-one by kidney tissue and isolated microsomes will be explored. We will investigate if metabolism of m-dioxane and its carcinogenic derivative, 2,6-dimethyl-4-acetoxy-m-dioxane, give rise to keto derivatives in analogy with p-dioxane. p-Dioxane-2-one will be tested for mutagenicity and the animal bioassay of its possible carcinogenic activity will be continued.